Vaccine halves dengue cases

[Another version of this article was first published on SciDev.Net. Click here for link.]


A vaccine that can half the number of dengue cases will soon be available. A recent trial conducted in Southeast Asia shows that this dengue vaccine achieves a vaccine efficacy of 56.5%: the vaccine reduces an individual’s chance of getting dengue by half. The vaccine is also safe to use as recipients did not suffer from any vaccine-related health complications.

Scientists created the vaccine by inserting surface proteins of dengue virus into a backbone of yellow fever virus non-structural proteins. The vaccine will “trigger an immune response in vaccinated individuals without causing the disease,” says Shamala Devi, medical immunologist at University of Malaya, Malaysia. This allows the immunity system to stage “an early defense against future dengue virus infections”.

This phase 3 trial recruited 10,275 children aged 2-14 years old in five Southeast Asian countries and randomly assigned them to receive either the vaccine or a placebo of saline solution. The children received three doses of the vaccine or placebo on months 0, 6 and 12, and were monitored until month 25.

“Weekly calls were made to the parents to determine the children’s well-being,” says Revathy Nallusamy, a paediatrician who coordinated the trial at Hospital Penang, Malaysia. If a child experienced high fever, doctors would check the child’s blood for dengue virus.

By month 25, scientists compared the incidences of dengue virus infection between the vaccinated and placebo-group. “Vaccine efficacy is the reduction in dengue cases in the vaccinated group compared to the placebo-group,” explains Annelies Wilder-Smith of Lee Kong Chian School of Medicine, Singapore. Wilder-Smith led an earlier trial of the same vaccine among adults in Singapore.

“It looks like a promising vaccine, but it is not perfect” says Wilder-Smith, who reacted to the trial results with “guarded optimism”. Wilder-Smith thinks that the vaccine efficacy of 56.5%, which sits between “very good” (>90%) and “bad” (<25%), “makes it difficult for policy-makers to decide if it is worthwhile to introduce this vaccine.”

Furthermore, the vaccine is effective against three of four identified dengue virus serotypes but fails to protect against serotype 2. An earlier phase 2b trial of the same vaccine in Thailand produced similar results against the serotypes. Serotype composition in a population changes over time, and all four serotypes exist in Southeast Asia.

Scientists were stunned by the vaccine’s weak efficacy against serotype 2. “Nobody would have predicted that,” says Wilder-Smith, “nobody.” Explaining the vaccine’s failure against serotype 2 “is now the one-billion dollar question,” she adds.

Population data show that younger children succumb more easily to dengue infection, and hence require better protection. However, the vaccine protects children aged 12-14 years old more (74.4% efficacy) than younger children of 2-5 years old (33.7% efficacy). The discrepancy might be because the vaccine works better on children who had prior dengue virus exposure (74.3% efficacy) than those without (35.5% efficacy). Older children in this study who might have had dengue infections would have also received better protection with the vaccine.

Now, another phase 3 trial of the same vaccine that involves more than 20,000 participants aged 9-16 years old in Latin America nears completion; the results will be published end of 2014. Wilder-Smith expects the Latin America trial to report similar and, due to the larger sample size, more reliable vaccine efficacy with less variation.

Sanofi Pasteur, the company that sponsored the vaccine development, has announced that the vaccine will be commercially available by July 2015. However, public health officers will have to consider the logistics and economics of introducing the vaccine. “Dengue costs the individual, and it also costs the healthcare system,” says Wilder-Smith.

As it stands, the current vaccine alone will not eradicate dengue from the more than 2.5 billion people living with the virus. “If you are going to vaccinate,” Shamala Devi emphasizes “continue all the other procedures with the same gusto and keep mosquito levels low.”

If a vaccine provides more than 75% efficacy, “there will be no doubt that you want to introduce it.” Unfortunately, “we still have a long way to go before” we get to that. “For the moment,” Wilder-Smith adds, “the Sanofi Pasteur vaccine with 56% efficacy is the best and only that we have.”

Capeding, M., Tran, N., Hadinegoro, S., Ismail, H., Chotpitayasunondh, T., Chua, M., Luong, C., Rusmil, K., Wirawan, D., Nallusamy, R., Pitisuttithum, P., Thisyakorn, U., Yoon, I., van der Vliet, D., Langevin, E., Laot, T., Hutagalung, Y., Frago, C., Boaz, M., Wartel, T., Tornieporth, N., Saville, M., & Bouckenooghe, A. (2014). Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial The Lancet DOI: 10.1016/S0140-6736(14)61060-6

Capeding et al. 2014. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. The Lancet. DOI: 10.1016/S0140-6736(14)61060-6.

Additional Reading

Dengue. World Health Organization.

First Dengue Vaccine ‘Shows Promise’. BBC. July 2014.

Dengue: A Continuing Threat. Nature Reviews Microbiology, 2010.



One thought on “Vaccine halves dengue cases

  1. Pingback: Treating school uniforms to reduce dengue: the Finances | Torch

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